Simultaneous plasma and oral fluid morphine and codeine concentrations after controlled administration of poppy seeds with known opiate content

Abstract

Opiates are included in drug testing programs because of their psychoactive properties and abuse potential, but excluding poppy seed ingestion is necessary to correctly interpret positive opiate results. There are few available data for plasma and oral fluid (OF) following poppy seed ingestion, and most do not report opiate content in the ingested poppy seeds. We quantified plasma and OF morphine and codeine concentrations via a fully validated liquid chromatography–tandem mass spectrometry method after controlled administration of two doses (8 h apart) of raw, uncooked poppy seeds (45-g) each containing 15.7 mg of morphine and 3.1 mg of codeine. Simultaneous specimens were collected before and up to 32 h after the first dose. Maximum OF morphine and codeine concentrations (3.6–110 and 2.1–22.4 µg/l, respectively) were significantly greater than simultaneously collected maximum plasma concentrations (2.8–9.3 and 1.1–2.0 µg/l, respectively). OF and plasma morphine and codeine concentrations were significantly correlated, but large variabilities preclude plasma concentration estimations from OF results. The median OF morphine time of first detection (tfirst) and time of last detection (tlast) were both 0.5 h with cutoffs from 20 to 40 µg/l, with 0.9–6.7 % positive specimens. Codeine was detected only at low 15–20 µg/l OF cutoffs; median tfirst and tlast were 0.5–1.3 h and 0.5–2.3 h, respectively, with only 0.4–1.8 % specimens positive. After two large, raw, uncooked poppy seed doses, significant differences between plasma and OF opiate pharmacokinetics were observed. Less than 6.7 % positive OF tests and a median morphine OF detection time of only 0.5 h with cutoffs from 20 to 40 µg/l suggest that few OF positive morphine tests can be explained by poppy seed ingestion.